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Purpose: The aim of this prospective study was to evaluate the clinical performance of zirconia-based posterior four-unit fixed dental prostheses (FDPs) after 4 years of clinical observation. Materials and Methods: Between 2006 and 2010, 10 patients (5 women, 5 men; mean age: 52.8 years) received 17 posterior four-unit FDPs. Two calibrated examiners evaluated the FDPs independently 1 week (baseline), 6 months, and 1, 2, 3, and 4 years after placement using California Dental Association (CDA) criteria. Periodontal status was assessed on both the abutment and contralateral control teeth using Plaque Index, Gingival Index, probing attachment level, and Margin Index parameters. Statistical analysis was performed using descriptive statistics and the Wilcoxon signed-rank test. Results: Three restorations were lost because of fractures at their distal connectors after a mean clinical service of 25.3 months, and one abutment tooth was extracted because of vertical root fracture 23 months after cementation. Three FDPs presented chipping of a moderate size 1 week before framework fracture, and minor chipping was observed in 2 other FDPs 1 week and 36 months after cementation. After 4 years of clinical service, the cumulative survival rate of the posterior four-unit FDPs was 76.5%. No caries lesions were detected on the abutment teeth. The remaining restorations were judged to be satisfactory according to the CDA criteria. Periodontal parameters did not show significant differences between test and control teeth, but Gingival Index scores demonstrated a slight increase in inflammation in the distal abutments after 4 years (P = .016). Conclusions: The use of zirconia-based posterior four-unit FDPs should be restricted for patients with high esthetic demands, except in patients where at least 4 mm of height is available for connector thickness. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the radiopacity of the core and veneer ceramics in four zirconia-based crown systems: In-Ceram Zirconia, In-Ceram YZ, Procera Zirconia, and Cercon. Two-millimeter-thick restoration slices were prepared and digitally radiographed alongside an aluminum stepwedge. The grayscale data were converted into millimeters of aluminum by an image analysis program. The two-way analysis of variance test detected significant differences with respect to all-ceramic system, layer ceramic, and the interaction of the two factors (P = .0001). All materials presented radiopacity values above the minimum recommended by the International Organization for Standardization. [ABSTRACT FROM AUTHOR]

The effect of germanium trapezoidal profile shape on the direct current (DC) current gain (βF), cut-off frequency (fT) and maximum oscillation frequency (fMAX) of silicon-germanium (SiGe) hetero-junction bipolar transistors (HBTs) has been investigated. The energy balance (EB), hydrodynamic (HD) and drift-diffusion (DD) physical transport models in SILVACO technology computer aided design (T-CAD) simulator were used. It was found that the current gain values using energy balance model are higher than hydrodynamic and much higher than those corresponding to drift-diffusion. Moreover, decreasing the germanium gradient slope towards the collector side of the base enhances the maximum oscillation frequencies using HD and EB models whilst, they remain stable for DD model.

Copyright of INMATEH - Agricultural Engineering is the property of INMATEH - Agricultural Engineering and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of INMATEH - Agricultural Engineering is the property of INMATEH - Agricultural Engineering and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In any application, the sizes of the particles to be removed from the mixtures heterogeneous determine, to a large extent, the method to be used for their separation. The literature reveals that the cyclone efficiency and implicitly the sedimentation rate is dependent on the particle size from the mass of heterogeneous solid-fluid mixtures. The objective of this paper is to theoretically demonstrate the influence of the solid particle dimensions on the sedimentation rate in centrifugal field, inside the cyclone and the time influence on sedimentation in the two sedimentary regimes. [ABSTRACT FROM AUTHOR]

This paper presents the manner of determining the cutting resistance force in the cutting process of certain vegetables. The role of this paper is to highlight the influence of the sharpening angle of single edged cutting knife. To achieve this experimental measurements were performed consisting of cutting samples of plant product using single edged knives with different sharpening angle, respectively 15°, 30°, 45°. The determination of the optimum cutting angle for different types of vegetables will lead to a lower energy consumption required for the cutting processes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the Fracture resistance of all ceramic crowns cemented on titanium and zirconia implant abutments. Material and Methods" Customized implant abutments For maxillary right central incisors made of-titanium (Ti) and zirconia (Zr) (n=60, n=30 per group) were Fabricated for an internal connection implant system. All-ceramic crowns were fabricated For their corresponding implant abutments using the Following systems (n=10 per group): (1) monolithic computer-aided design/computer-assisted manufacture (CAD/CAM) lithium disilicate (MLD); (2) pressed lithium disilicate (PLD); (:3) yttrium stabilized tetragonal zirconia polycrystal (YTZP). The Frameworks of both PLD and YTZP systems were manually veneered with a fluorapatite-based ceramic. The crowns were adhesively cemented to their implant abutments and loaded to Fracture in a universal testing machine (0.5 mm/minute). Data were analyzed using two-way analysis of variance (ANOVA) and Tukey's test (α=0.05). Results: Both the abutment material (P=.0001) and the ceramic crown system (P=.028) significantly affected the results. Interaction terms were not significant (P=.598). Ti-MLD (558.5±35 N) showed the highest mean fracture resistance among all abutment-crown combinations (±340.3±62-495.9±53 N) (P<.05). Both MLD and veneered ceramic systems in combination with Ti abutments (558.5±35-495.9±53 N) presented significantly higher values than with Zr abutments (392.9±55-340.3±62 N) (P<.05). MLD crown system showed significantly higher mean Fracture resistance compared to manually veneered ones on both Ti and Zr abutments (P<.0S). While Ti-MLD and Ti-PLD abutment-crown combinations Failed only in the crowns without abutment Fractures, Zr-YTZP combination failed exclusively in the abutment without crown Fracture. Zr-MLD and Zr-PLD failed predominantly in both the abutment and the crown. Ti-YTZP showed only implant neck distortion. Conclusions: The highest Fracture resistance was obtained with titanium abutments restored with MLD crowns, but the Failure type was more Favorable with Ti-YTZP combination. [ABSTRACT FROM AUTHOR]

Bacillus thuringiensis crystal (Cry) proteins have been expressed in commercial transgenic crops for nearly 30 years, providing safe and effective control of insect pests and significantly reducing the application of hazardous chemical pesticides. B. thuringiensis crystal proteins have also been shown to target parasitic nematodes, including plant parasitic nematodes. Recently, transgenic soybean crops expressing Cry14Ab have been shown to provide control against the soybean cyst nematode Heterodera glycines, marking the first time a crystal protein is being commercialized in transgenic crops for control of a nematode pest. However, apart from H. glycines and the free-living nematode, Caenorhabditis elegans, the breadth of nematode activity of Cry14Ab, e.g., against gastrointestinal parasitic nematodes (GINs), has not been reported. Here we study the efficacy of Cry14Ab against a wide range of gastrointestinal nematode parasites (GINs) in vitro and in vivo. We find that Cry14Ab is effective in vitro against the barber's pole worm Haemonchus contortus larvae, small strongyles cyathostomin larvae, the hookworm Ancylostoma ceylanicum adults, the roundworm Ascaris suum L4 larvae, and the whipworm Trichuris muris adults. In rodents infected with GIN parasites, Cry14Ab is effective as an in vivo anthelmintic against the hookworms A. ceylanicum and N. americanus, against the mouse parasite Heligmosomoides polygyrus bakeri, and against the roundworm A. suum. Cry14Ab also variably reduces the reproduction of the whipworm T. muris in vivo. Using optimized profile Markov Models, we looked for other putative anthelmintic Cry proteins and, within this list, identified a Bt crystal protein, GenBank accession no. MF893203, that we produced and demonstrated intoxicated GINs. This protein, with 90% amino acid identity to Cry14Ab, is active against C. elegans, A. ceylanicum adults, and A. suum L4 larvae in vitro. MF893203 was given the official designation of Cry14Ac. Cry14Ac is also an effective in vivo anthelmintic against A. ceylanicum hookworms in hamsters and intestinal A. suum in mice. Taken together, our results demonstrate that Cry14Ab and Cry14Ac have wide therapeutic utility against GINs., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: The University of Massachusetts Chan Medical School is pursuing patent protection related to the use of Cry14Ab as anthelmintic via U.S. Provisional Patent Application Serial No. 63/439,759 (K.F. and R.V.A. as inventors) and the University of Massachusetts Chan Medical School and University of Göttingen are pursing patent protection related to the use of Cry14Ac as anthelmintic via U.S. Provisional Patent Application Serial No. 63/649,526 (K.F., S.D.V., H.L., and R.V.A. as inventors)., (Copyright: © 2024 Hoang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To compare the implant-abutment connection microgap between computer-aided design and computer-aided manufacturing (CAD/CAM) milled or laser-sintered cobalt-chrome custom abutments with or without ceramic veneering and titanium stock abutments with or without crown cementation., Material and Methods: Six groups of six abutments each were prepared: (1) CAD/CAM cobalt-chrome custom abutments: milled, milled with ceramic veneering, laser-sintered, and laser-sintered with ceramic veneering (four groups: MIL, MIL-C, SIN, and SIN-C, respectively) and (2) titanium stock abutments with or without zirconia crown cementation (two groups: STK and STK-Z, respectively). Abutments were screwed to the implants by applying 30 Ncm torque. All 36 samples were sectioned along their long axes. The implant-abutment connection microgap was measured using scanning electron microscopy on the right and left sides of the connection at the upper, middle, and lower levels. Data were analyzed using the Kruskal-Wallis test (p < .05)., Results: Mean values (μm) of the microgap were 0.54 ± 0.44 (STK), 0.55 ± 0.48 (STK-Z), 1.53 ± 1.30 (MIL), 2.30 ± 2.2 (MIL-C), 1.53 ± 1.37 (SIN), and 1.87 ± 1.8 (SIN-C). Although significant differences were observed between the STK and STK-Z groups and the other groups (p < .05), none were observed between the milled and laser-sintered groups before or after ceramic veneering. The largest microgap was observed at the upper level in all groups., Conclusions: Titanium stock abutments provided a closer fit than cobalt-chrome custom abutments. Neither crown cementation nor ceramic veneering resulted in significant changes in the implant-abutment connection microgap., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: This study aimed to assess the fit of interim crowns produced using DLP-based 3D printing with different manufacturing workflows-open and proprietary-versus milling technology., Methods: A total of 120 crowns were evaluated using the replica technique. The control group (Mill, n = 30) was manufactured via subtractive technology. Experimental groups were printed using a DLP printer (SprintRay Pro95). In the proprietary mode (SR100, n = 30), manufacturer resin was used with a 100-μm layer thickness (LT) and a splashing cleaning postprocessing. In the open mode, validated resin was used. Group B100 (n = 30) had a 100-μm LT, and group B50 (n = 30) had a 50-μm followed by postprocessing in an ultrasonic bath with full immersion in isopropyl alcohol. Kruskal-Wallis tests with Bonferroni correction was applied after normal analysis (α = 0.05)., Results: Group B50 exhibited the best overall fit (123.87 ± 67.42 μm), which was comparable to the gold standard Milling group, which demonstrated the lowest marginal fit (p = 0.760). SR100 showed significantly poorer performance compared to Mill, B50, and B100 (p < 0.001)., Conclusions: 3D printed and milled interim crowns generally demonstrated clinically acceptable fit, with the exception of the SR100 group. Postprocessing notably influenced crown fit, with the open mode with total immersion in isopropyl alcohol being superior., Clinical Significance: The present study demonstrates that the selection of an optimal manufacturing and postprocessing workflow results in superior fit for interim crowns. This enables dental professionals to evaluate protocols and ensure reliable outcomes with improved clinical outcomes in interim crown fabrication., (© 2024 The Author(s). Journal of Esthetic and Restorative Dentistry published by Wiley Periodicals LLC.)

Objectives: This scoping review aimed to identify the available evidence in the use of 3D printing technology in dental implantology. Due to the broad scope of the subject and its application in implantology, three main areas of focus were identified: (1) customized dental implants, (2) manufacturing workflow for surgical implant guides, and (3) related implant-supported prostheses factors, which include the metallic primary frameworks, secondary ceramic or polymer superstructures, and 3D implant analog models., Materials and Methods: Online databases (Medline, Cochrane, Embase, and CINAHL) were used to identify the studies published up to February 2023 in English. Two experienced reviewers performed independently the screening and selection among the 1737 studies identified. The articles evaluated the additive manufacturing (AM) technology, materials, printing, and post-processing parameters regarding dental implantology., Results: The 132 full-text studies that met the inclusion criteria were examined. Thirteen studies of customized dental implants, 22 studies about the workflow for surgical implant guides, and 30 studies of related implant-supported prostheses factors were included., Conclusions: (1) The clinical evidence about AM titanium and zirconia implants is scarce. Early data on survival rates, osseointegration, and mechanical properties are being reported. (2) 3D printing is a proven manufacturing technology to produce surgical implant guides. Adherence to the manufacturer's instructions is crucial and the best accuracy was achieved using MultiJet printer. (3) The quality of 3D printed prosthetic structures and superstructures is improving remarkably, especially on metallic alloys. However, better marginal fit and mechanical properties can be achieved with milling technology for metals and ceramics., (© 2023 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Addressing the growing problem of antifungal resistance in medicine and agriculture requires the development of new drugs and strategies to preserve the efficacy of existing fungicides. One approach is to utilize delivery technologies. Yeast particles (YPs) are 3-5 µm porous, hollow microspheres, a byproduct of food-grade Saccharomyces cerevisiae yeast extract manufacturing processes and an efficient and flexible drug delivery platform. Here, we report the use of YPs for encapsulation of tetraconazole (TET) and prothioconazole (PRO) with high payload capacity and stability. The YP PRO samples were active against both sensitive and azole-resistant strains of Candida albicans . The higher efficacy of YP PRO versus free PRO is due to interactions between PRO and saponifiable lipids in the YPs. Encapsulation of PRO in glucan lipid particles (GLPs), a highly purified form of YPs that do not contain saponifiable lipids, did not result in enhanced PRO activity. We evaluated the co-encapsulation of PRO with a mixture of the terpenes: geraniol, eugenol, and thymol. Samples co-encapsulating PRO and terpenes in YPs or GLPs were active on both sensitive and azole-resistant C. albicans . These approaches could lead to the development of more effective drug combinations co-encapsulated in YPs for agricultural or GLPs for pharmaceutical applications.

Introduction: The aim of this systematic review was to assess the literature reporting on the failure rates, survival rates and complication rates and patient reported outcome measures (PROMs) of anterior full (FC) or partial (PC) coverage single tooth restorations after a mean observation period of at least 3 years., Methods: Systematic search was conducted using the electronic databases: MEDLINE, EMBASE and Cochrane library. Data regarding survival (restoration failure) and complication rates and PROMs were extracted and presented descriptively., Results: Altogether 42 studies were included in the analysis (28 with FC, 12 with PC and 2 with both types of restorations). For FC restorations the estimated annual failure rate was 0.72 (95%CI: 0.33-1.57), resulting in a 5-year survival rate of 96.4% (95%CI: 92.4-98.3). For PC restorations, the estimated annual failure rate was 0.62 (95%CI: 0.27-1.46), resulting in a 5-year survival rate of 96.9% (95%CI: 93.0-98.7). There was no significant difference between the groups regarding survival or technical complications, while significantly fewer biological complications were observed with PC compared to FC restorations (test for subgroup differences, p=0.01)., Conclusions: FC and PC restorations showed high 5-year survival rates but the teeth restored with FC restorations may be more prone to biological complications., (Copyright© 2023 Dennis Barber Ltd.)

Purpose: The aim of this randomized controlled clinical trial was to evaluate peri-implant marginal bone levels (MBLs) and soft tissue dimension changes 1 year after loading. Patients in the control group received bone-level implants, whereas in the test group, tissue-level implants with a convergent transmucosal neck were used., Material and Methods: MBLs were calculated by measuring the distance from the implant shoulder to the first visible bone-to-implant contact using standardized periapical digital radiographs. Baseline (day of loading) and follow-up digital models obtained with an intraoral scanner were used to quantify the changes in the peri-implant soft tissue dimensions with a best-fit algorithm., Results: The difference between final and baseline MBLs showed a mean bone loss of 0.16 ± 0.01 mm in the test group (n = 15) and 0.45 ± 0.09 mm in the control group (n = 14) (p > 0.05). Soft tissue contour at the level of the gingival margin (GM) increased by 1.96 ± 2.69 mm in the test group and 0.65 ± 0.42 mm in the control group (p = 0.167). Both groups showed a coronal displacement of the gingival margin with no significant differences among them., Conclusions: The present study demonstrated peri-implant hard and soft tissues stability at both implant designs with no significant differences 12 months after loading., Clinical Relevance: There is still insufficient scientific evidence to demonstrate the role and advantages of the convergent transmucosal neck on the behavior of the peri-implant soft and hard tissues stability compared to a straight neck in bone-level implants 12 months after loading., (© 2023. The Author(s).)

Glucan particles (GPs) are hollow, porous microspheres derived from Saccharomyces cerevisiae (Baker's yeast). The hollow cavity of GPs allows for efficient encapsulation of different types of macromolecules and small molecules. The β-1,3-D-glucan outer shell provides for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors and uptake of particles containing encapsulated proteins elicit protective innate and acquired immune responses against a wide range of pathogens. A limitation of the previously reported GP protein delivery technology is limited protection from thermal degradation. Here we present results of an efficient protein encapsulation approach using tetraethylorthosilicate (TEOS) to lock protein payloads in a thermostable silica cage formed in situ inside the hollow cavity of GPs. The methods for this improved, efficient GP protein ensilication approach were developed and optimized using bovine serum albumin (BSA) as model protein. The improved method involved controlling the rate of TEOS polymerization, such that the soluble TEOS-protein solution was able to be absorbed into the GP hollow cavity before the protein-silica cage polymerized and becomes too large to transverse across the GP wall. This improved method provided for >90% GP encapsulation efficiency, increased thermal stabilization of GP ensilicated BSA, and was shown to be applicable for encapsulation of proteins of different molecular weights and isoelectric points. To demonstrate the retention of bioactivity of this improved method of protein delivery, we evaluated the in vivo immunogenicity of two GP ensilicated vaccine formulations using (1) ovalbumin as a model antigen and (2) a protective antigenic protein from the fungal pathogen Cryptococcus neoformans. The results show that the GP ensilicated vaccines have a similar high immunogenicity as our current GP protein/hydrocolloid vaccines, as evidenced by robust antigen-specific IgG responses to the GP ensilicated OVA vaccine. Further, a GP ensilicated C. neoformans Cda2 vaccine protected vaccinated mice from a lethal pulmonary infection of C. neoformans., Competing Interests: Declaration of Competing Interest GRO and ERS are inventors of US Patent App. 63/393,490, A Nano-Silica-In-Yeast Particle (YP) Drug Encapsulation Approach for Improved Thermal and Hydrolase Stability of YP Drug Delivery Formulations assigned to University of Massachusetts Medical School. The patent is managed by the Office of Technology Management and the Conflicts of Interest policies of the University of Massachusetts. The other authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: To determine whether the use of single or combined mechanical and virtual articulators, as well as facebows, jaw motion trackers, face scanners, and related devices, actually improve the efficacy of the prosthesis obtained in terms of lifespan and patient-related outcomes. To coin the terms Analogic and Digital Virtual Patients (AVP and DVP) as an attempt to analyze, clarify and synthesize terminology and workflows related to previously so-called devices., Materials and Methods: A scoping review was accomplished involving different databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-ScR) checklist and JBI guidance were followed to extract data regarding the Population, Context and Concept established., Results: Available literature on the efficacy of using devices and techniques related to both AVP and DVP workflows showed arguable study designs, great heterogeneity, and questionable quality., Conclusions: The terms AVP and DVP have been coined as a first step to clarify and simplify concepts and workflows related to the use of both mechanical and virtual articulators, as well as facebows, or facial and intraoral scanners, among others. This scoping review cannot claim that an AVP approach leads to more effective and efficient prosthetic restorations., (Copyright© 2023 Dennis Barber Ltd.)

Terpenes and essential oils are materials of great commercial use due to their broad spectra of antibacterial, antifungal, membrane permeation enhancement and antioxidant biological properties, as well as for their use as flavors and fragrances. Yeast particles (YPs) are 3-5 µm hollow and porous microspheres, a byproduct of some food-grade yeast ( Saccharomyces cerevisiae) extract manufacturing processes, that have been used for the encapsulation of terpenes and essential oils with high payload loading capacity (up to 500% weight) and efficiency, providing stability and sustained-release properties. This review focuses on encapsulation approaches for the preparation of YP-terpene and essential oil materials that have a wide range of potential agricultural, food and pharmaceutical applications.

Bacillus thuringiensis (Bt) is a Gram-positive soil bacterium that is widely and safely applied in the environment as an insecticide for combatting insect pests that damage crops or are disease vectors. Dominant active ingredients made by Bt are insect-killing crystal (Cry) proteins released as crystalline inclusions upon bacterial sporulation. Some Bt Cry proteins, e.g., Cry5B (formally Cry5Ba1), target nematodes (roundworms) and show exceptional promise as anthelmintics (cures for parasitic nematode diseases). We have recently described inactivated bacteria with cytosolic crystal(s) (IBaCC) in which bioactive Bt Cry crystals (containing Cry5B) are fully contained within the cytosol of dead bacterial ghosts. Here, we demonstrate that these IBaCC-trapped Cry5B crystals can be liberated and purified away from cellular constituents, yielding purified cytosolic crystals (PCC). Cry5B PCC contains ~95% Cry5B protein out of the total protein content. Cry5B PCC is highly bioactive against parasitic nematode larvae and adults in vitro . Cry5B PCC is also highly active in vivo against experimental human hookworm and Ascaris infections in rodents. The process was scaled up to the 100-liter scale to produce PCC for a pilot study to treat two foals infected with the ascarid Parascaris spp. Single-dose Cry5B PCC brought the fecal egg counts of both foals to zero. These studies describe the process for the scalable production of purified Bt crystals and define a new and attractive pharmaceutical ingredient form of Bt Cry proteins. IMPORTANCE Bacillus thuringiensis crystal proteins are widely and safely used as insecticides. Recent studies have shown they also can cure gastrointestinal parasitic worm (nematode) infections when ingested. However, reproducible, scalable, and practical techniques for purifying these proteins have been lacking. Here, we address this severe limitation and present scalable and practical methods for large-scale purification of potently bioactive B. thuringiensis crystals and crystal proteins. The resultant product, called purified cytosolic crystals (PCC), is highly compatible with ingestible drug delivery and formulation. Furthermore, there are growing applications in agriculture and insect control where access to large quantities of purified crystal proteins is desirable and where these methods will find great utility.

Yeast particles (YPs) are 3−5 µm hollow and porous microspheres, a byproduct of some food grade yeast (Saccharomyces cerevisiae) extract manufacturing processes. Terpenes can be efficiently encapsulated inside YPs by passive diffusion through the porous cell walls. As previously published, this YP terpene encapsulation approach has been successfully implemented (1) to develop and commercialize fungicide and nematicide products for agricultural applications, (2) to co-load high potency agrochemical actives dissolved in terpenes or suitable solvents, and (3) to identify YP terpenes with broad-acting anthelmintic activity for potential pharmaceutical applications. These first-generation YP terpene materials were developed with a <2:1 terpene: YP weight ratio. Here we report methods to increase the terpene loading capacity in YPs up to 5:1 terpene: YP weight ratio. Hyper-loaded YP terpenes extend the kinetics of payload release up to three-fold compared to the commercialized YP terpene formulations. Hyper-loaded YP-terpene compositions were further optimized to achieve high terpene storage encapsulation stability from −20 °C to 54 °C. The development of hyper-loaded YP terpenes has a wide range of potential agricultural and pharmaceutical applications with terpenes and other compatible active substances that could benefit from a delivery system with a high payload loading capacity combined with increased payload stability and sustained release properties.

The aim of this study was to evaluate the diagnostic reliability of a web-based artificial intelligence program for the detection of interproximal caries in bitewing radiographs. Three hundred bitewing radiographs of patients were subjected to the evaluation of a convolutional neural network. First, the images were visually evaluated by a previously trained and calibrated operator with radiodiagnosis experience. Then, ground truth was established and was clinically validated. For enamel caries, clinical assessment included a combination of clinical-visual and radiography evaluations. For dentin caries, clinical validation was performed by instrumentally accessing the cavity. Second, the images were uploaded and analyzed by the web-based software. Four different models were established to analyze its evaluations according to the confidence threshold (0-100%) offered by the program: model 1 (values >0% were considered positive and values of 0% were considered negative), model 2 (values ≥25% were considered positive and values <25% were considered negative), model 3 (values ≥50% were considered positive and values <50% were considered negative), and model 4 (values ≥75% were considered positive and values <75% were considered negative). The accuracy rate (A), sensitivity (S), specificity (E), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and areas under receiver operating characteristic curves (AUC) were calculated for the four models of agreement with the software. Models showed the following results respectively: A = 70.8%, 82%, 85.6%, 86.1%; S = 87%, 69.8%, 57%, 41.6%; E = 66.3%, 85.4%, 93.7%, 98.5%; PPV = 42%, 57.2%, 71.6%, 88.6%; NPV = 94.8%, 91%, 88.6%, 85.8%; PLR = 2.58, 4.78, 9.05, 27.73; NLR = 0.2, 0.35, 0.46, 0.59; AUC = 0.767, 0.777, 0.753, 0.701. Findings in the present study suggest that the artificial intelligence web-based software provides a good diagnostic reliability on the detection of dental caries. Our study highlighted model 2 for showing the best results to differentiate between healthy teeth and decayed teeth., (© 2022 S. Karger AG, Basel.)

Purpose To evaluate the effect of different cleaning methods on the shear bond strength (SBS) of a 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-containing self-adhesive resin cement to zirconia after saliva contamination.Methods Sixty zirconia specimens were randomly divided into four groups (n=15) according to treatment surface. Except for the control group, all samples were contaminated with saliva and were then rinsed with water-spray and air-dried. Subsequently, the specimens were either treated with a cleaning paste (CP), with argon plasma (AP), or did not undergo an additional cleaning process (WS). An MDP-containing self-adhesive resin cement was applied onto the ceramic surfaces. Specimens were stored in water (24 hours) followed by thermocycling (5°C to 55°C for 10.000 cycles). SBS tests were performed in a universal testing machine, and the results (MPa ± SD) were statistically analyzed using ANOVA and Bonferroni post-hoc test. Fractured surfaces were examined to identify the failure types using a stereomicroscopy and SEM.Results The surface cleaning treatment (p<0.05) significantly affected the results. The highest SBS values were observed in the control group (12.16 ± 1.22 MPa) and were statistically comparable to values for the CP group (11.38 ± 1.65 MPa). The AP group (9.17 ± 1.06 MPa) showed significantly higher bond strength than the WS group (6.95 ± 1.20 MPa), but it showed significantly lower strength than the control and CP groups.Conclusions The CP application was the most effective method in removing saliva contamination. The AP treatment could not restore the SBS to the same level as uncontaminated specimens.

Terpenes are naturally occurring compounds produced by plants that are of great commercial interest in the food, agricultural, cosmetic, and pharmaceutical industries due to their broad spectra of antibacterial, antifungal, anthelmintic, membrane permeation enhancement, and antioxidant biological activities. Applications of terpenes are often limited by their volatility and the need for surfactants or alcohols to produce stable, soluble (non-precipitated) products. Yeast particles (YPs) are hollow, porous microspheres that have been used for the encapsulation of terpenes (YP terpenes) by passive diffusion of terpenes through the porous YP cell walls. We here report the development of a second generation YP encapsulated terpene technology that incorporates the stimuli-responsive control of terpene release using biodegradable pro-terpene compounds (YP pro-terpenes). YP terpenes and YP pro-terpenes were both produced, in which high levels of carvacrol, eugenol, thymol and geraniol were encapsulated. The YP pro-terpenes show higher encapsulation stability than YP terpenes due to pro-terpenes being non-volatile solids at room temperature and stable in suspensions at neutral pH. YP pro-terpenes and YP terpenes were evaluated for biological activity in antibacterial, antifungal and anthelmintic assays. The YP pro-terpenes retained the full biological activity of the parent terpene compound.

Ascaris and Parascaris are important parasites in the family Ascarididae, large, ubiquitous intestinal-dwelling nematodes infecting all classes of vertebrates. Parasitic nematode drug resistance in veterinary medicine and drug recalcitrance in human medicine are increasing worldwide, with few if any new therapeutic classes on the horizon. Some of these parasites are zoonotic, e.g. , Ascaris is passed from humans to pigs and vice versa . The development of new therapies against this family of parasites would have major implications for both human and livestock health. Here we tested the therapeutic ability of a paraprobiotic or dead probiotic that expresses the Bacillus thuringiensis Cry5B protein with known anthelmintic properties, against zoonotic Ascaris suum and Parascaris spp. This paraprobiotic, known as IBaCC, intoxicated A. suum larvae in vitro and was highly effective in vivo against intestinal A. suum infections in a new mouse model for this parasite. Fermentation was scaled up to 350 l to treat pigs and horses. Single dose Cry5B IBaCC nearly completely cleared A. suum infections in pigs. Furthermore, single dose Cry5B IBaCC drove fecal egg counts in Parascaris -infected foals to zero, showing at least parity with, and potential superiority to, current efficacy of anthelmintics used against this parasite. Cry5B IBaCC therefore represents a new, paraprobiotic One Health approach towards targeting Ascarididae that is safe, effective, massively scalable, stable, and useful in human and veterinary medicine in both the developed and developing regions of the world., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

The high global burden of cryptococcosis has made development of a protective vaccine a public health priority. We previously demonstrated that a vaccine composed of recombinant Cryptococcus neoformans chitin deacetylase 2 (Cda2) delivered in glucan particles (GPs) protects BALB/c and C57BL/6 mice from an otherwise lethal challenge with a highly virulent C. neoformans strain. An immunoinformatic analysis of Cda2 revealed a peptide sequence predicted to have strong binding to the major histocompatibility complex class II (MHC II) H2-IAd allele found in BALB/c mice. BALB/c mice vaccinated with GPs containing a 32-amino-acid peptide (Cda2-Pep1) that included this strong binding region were protected from cryptococcosis. Protection was lost with GP-based vaccines containing versions of recombinant Cda2 protein and Cda2-Pep1 with mutations predicted to greatly diminish MHC II binding. Cda2 has homology to the three other C. neoformans chitin deacetylases, Cda1, Cda3, and Fpd1, in the high-MHC II-binding region. GPs loaded with homologous peptides of Cda1, Cda3, and Fpd1 protected BALB/c mice from experimental cryptococcosis, albeit not as robustly as the Cda2-Pep1 vaccine. Finally, seven other peptides were synthesized based on regions in Cda2 predicted to contain promising CD4 + T cell epitopes in BALB/c or C57BL/6 mice. While five peptide vaccines significantly protected BALB/c mice, only one protected C57BL/6 mice. Thus, GP-based vaccines containing a single peptide can protect mice against cryptococcosis. However, given the diversity of human MHC II alleles, a peptide-based Cryptococcus vaccine for use in humans would be challenging and likely need to contain multiple peptide sequences. IMPORTANCE Cryptococcosis, due to infection by fungi of the Cryptococcus neoformans species complex, is responsible for substantial morbidity and mortality in immunocompromised persons, particularly those with AIDS. Cryptococcal vaccines are a public health priority yet are not available for human use. We previously demonstrated mice could be protected from experimental cryptococcosis with vaccines composed of recombinant cryptococcal proteins encased in hollow highly purified yeast cell walls (glucan particles). In this study, we examined one such protective protein, Cda2, and using bioinformatics, we identified a region predicted to stimulate strong T cell responses. A peptide containing this region formulated in glucan particle-based vaccines protected mice as well as the recombinant protein. Other peptide vaccines also protected, including peptides containing sequences from proteins homologous to Cda2. These preclinical mouse studies provide a proof of principle that peptides can be effective as vaccines to protect against cryptococcosis and that bioinformatic approaches can guide peptide selection.

Gastrointestinal nematodes (GINs) of humans, e.g., hookworms, negatively impact childhood growth, cognition, nutrition, educational attainment, income, productivity, and pregnancy. Hundreds of millions of people are targeted with mass drug administration (MDA) of donated benzimidazole anthelmintics. However, benzimidazole efficacy against GINs is suboptimal, and reduced/low efficacy has been seen. Developing an anthelmintic for human MDA is daunting: it must be safe, effective, inexpensive, stable without a cold chain, and massively scalable. Bacillus thuringiensis crystal protein 5B (Cry5B) has anthelmintic properties that could fill this void. Here, we developed an active pharmaceutical ingredient (API) containing B. thuringiensis Cry5B compatible with MDA. We expressed Cry5B in asporogenous B. thuringiensis during vegetative phase, forming cytosolic crystals. These ba cteria with c ytosolic c rystals (BaCC) were rendered inviable (inactivated BaCC [IBaCC]) with food-grade essential oils. IBaCC potency was validated in vitro against nematodes. IBaCC was also potent in vivo against human hookworm infections in hamsters. IBaCC production was successfully scaled to 350 liters at a contract manufacturing facility. A simple fit-for-purpose formulation to protect against stomach digestion and powdered IBaCC were successfully made and used against GINs in hamsters and mice. A pilot histopathology study and blood chemistry workup showed that five daily consecutive doses of 200 mg/kg body weight Cry5B IBaCC (the curative single dose is 40 mg/kg) was nontoxic to hamsters and completely safe. IBaCC is a safe, inexpensive, highly effective, easy-to-manufacture, and scalable anthelmintic that is practical for MDA and represents a new paradigm for treating human GINs., (Copyright © 2021 Li et al.)

Haemonchus contortus is a critical parasite of goats and sheep. Infection by this blood-feeding gastrointestinal nematode (GIN) parasite has significant health consequences, especially in lambs and kids. The parasite has developed resistance to virtually all known classes of small molecule anthelmintics used to treat it, giving rise in some areas to multidrug resistant parasites that are very difficult to control. Thus, new anthelmintics are urgently needed. Bacillus thuringiensis (Bt) crystal protein 5B (Cry5B), a naturally occurring protein made by a bacterium widely and safely used around the world as a bioinsecticide, represents a new non-small molecule modality for treating GINs. Cry5B has demonstrated anthelmintic activities against parasites of monogastric animals, including some related to those that infect humans, but has not yet been studied in a ruminant. Here we show that H. contortus adults are susceptible to Cry5B protein in vitro. Cry5B produced in its natural form as a spore-crystal lysate against H. contortus infections in goats had no significant efficacy. However, a new Active Pharmaceutical Ingredient (API) paraprobiotic form of Cry5B called IBaCC (Inactivated Bacterium with Cytosolic Crystals), in which Cry5B crystals are encapsulated in dead Bt cell wall ghosts, showed excellent efficacy in vitro against larval stages of H. contortus and relative protein stability in bovine rumen fluid. When given to sheep experimentally infected with H. contortus as three 60 mg/kg doses, Cry5B IBaCC resulted in significant reductions in fecal egg counts (90%) and parasite burdens (72%), with a very high impact on female parasites (96% reduction). These data indicate that Cry5B IBaCC is a potent new treatment tool for small ruminants in the battle against H. contortus., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the two Drosophila NF-κB signaling pathways, Imd and Toll. Antimicrobial peptide (AMP) gene induction downstream of either pathway is suppressed when cells infected with IIV-6 are also stimulated with Toll or Imd ligands. We find that cleavage of both Imd and Relish, as well as Relish nuclear translocation, three key points in Imd signal transduction, occur in IIV-6 infected cells, indicating that the mechanism of viral inhibition is farther downstream, at the level of Relish promoter binding or transcriptional activation. Additionally, flies co-infected with both IIV-6 and the Gram-negative bacterium, Erwinia carotovora carotovora , succumb to infection more rapidly than flies singly infected with either the virus or the bacterium. These findings demonstrate how pre-existing infections can have a dramatic and negative effect on secondary infections, and establish a Drosophila model to study confection susceptibility., Competing Interests: The authors declare no conflict of interest

Purpose: To compare the surface roughness and biaxial flexural strength of dental ceramics obtained after chairside surface modification by mechanical polishing procedures, versus laboratory reglazing., Materials and Methods: Discs (16 × 1.5 ± 1.6 mm) (N = 90) of various framework-veneering combinations were fabricated: D/FC: lithium disilicate/feldspathic ceramic; Z/AL: zirconium dioxide/aluminous ceramic; N/FC: noble alloy/feldspathic ceramic; N/FF: noble alloy feldspathic with fluorapatite; B/FC: base alloy/feldspathic ceramic; B/FF: base alloy/feldspathic ceramic with fluorapatite. In each group 10 specimens were ground using a diamond bur (46 μm) and five were polished with silicone-reinforced disc polishers (25 μm). Surface roughness (Ra) was measured using contact profilometry. After thermocycling in artificial saliva (6000 cycles, 5 to 55 ± 5°C), biaxial flexural strength was measured using "piston-on-three ball" test. The data (N) were analyzed using one-way ANOVA, Bonferroni, and Tukey's posthoc tests. Weibull distribution values were calculated., Results: Surface roughness was significantly higher in the ground group only (p < 0.0001). Mean fracture toughness was significantly lower for chipping (RK: 287, HS: 22, ISO: 1099 MPa) than for total fracture (p < 0.05), (RK: 841, HS:64, ISO: 3222 MPa). For chipping, Weibull distribution presented the highest shape value (m) for D/FC (3.82-5.07) and for total fracture for B/FC (3.69-4.6)., Conclusion: Chairside surface polishing restored veneer ceramic roughness and mechanical strength to the level of glazing. Feldspathic ceramic with fluorapatite presented better polishing results than conventional feldspathic ceramic did. Ceramic fused to metal was more resistant than lithium disilicate or zirconium dioxide framework-veneer assemblies. Lithium disilicate framework veneered with feldspathic ceramic presented more durability against chipping., Clinical Implications: After chairside occlusal modifications in the surfaces of cemented all-ceramic or fused-to-metal FDPs, mechanical polishing procedures should always be carried out., (© 2017 by the American College of Prosthodontists.)

Background: Drosophila is a powerful model for the study of factors modulating innate immunity. This study examines the effect of water-loss dehydration on innate immune responsiveness in the Drosophila renal system (Malpighian tubules; MTs), and how this leads to elevated host defense and contributes to immunosenescence., Results: A short period of desiccation-elevated peptidoglycan recognition protein-LC (PGRP-LC) expression in MTs, increased antimicrobial peptide (AMP) gene induction, and protected animals from bacterial infection. We show that desiccation increased ecdysone synthesis in MTs, while inhibition of ecdysone synthesis or ecdysone receptor expression, specifically within MTs, prevented induction of PGRP-LC and reduced protection from bacterial infection. Additionally, aged flies are constitutively water-stressed and have elevated levels of ecdysone and PGRP-LC. Conversely, adults aged at high relative humidity show less water loss and have reduced expression of PGRP-LC and AMPs., Conclusions: The Drosophila renal system is an important contributor to host defense and can modulate immune responses in an organ autonomous manner, responding to environmental changes such as desiccation. Desiccation primes immune responsiveness by elevating PGRP-LC expression specifically in MTs. In response to desiccation, ecdysone is produced in MTs and acts in a paracrine fashion to increase PGRP-LC expression, immune responsiveness, and improve host defense. This activity of the renal system may contribute to the immunosenescence observed in Drosophila.

Dementia with Lewy bodies, Parkinson's disease, and Multiple System Atrophy are age-related neurodegenerative disorders characterized by progressive accumulation of α-synuclein (α-syn) and jointly termed synucleinopathies. Currently, no disease-modifying treatments are available for these disorders. Previous preclinical studies demonstrate that active and passive immunizations targeting α-syn partially ameliorate behavioral deficits and α-syn accumulation; however, it is unknown whether combining humoral and cellular immunization might act synergistically to reduce inflammation and improve microglial-mediated α-syn clearance. Since combined delivery of antigen plus rapamycin (RAP) in nanoparticles is known to induce antigen-specific regulatory T cells (Tregs), we adapted this approach to α-syn using the antigen-presenting cell-targeting glucan microparticle (GP) vaccine delivery system. PDGF-α-syn transgenic (tg) male and female mice were immunized with GP-alone, GP-α-syn (active humoral immunization), GP+RAP, or GP+RAP/α-syn (combined active humoral and Treg) and analyzed using neuropathological and biochemical markers. Active immunization resulted in higher serological total IgG, IgG1, and IgG2a anti-α-syn levels. Compared with mice immunized with GP-alone or GP-α-syn, mice vaccinated with GP+RAP or GP+RAP/α-syn displayed increased numbers of CD25-, FoxP3-, and CD4-positive cells in the CNS. GP-α-syn or GP+RAP/α-syn immunizations resulted in a 30-45% reduction in α-syn accumulation, neuroinflammation, and neurodegeneration. Mice immunized with GP+RAP/α-syn further rescued neurons and reduced neuroinflammation. Levels of TGF-β1 were increased with GP+RAP/α-syn immunization, while levels of TNF-α and IL-6 were reduced. We conclude that the observed effects of GP+RAP/α-syn immunization support the hypothesis that cellular immunization may enhance the effects of active immunotherapy for the treatment of synucleinopathies. SIGNIFICANCE STATEMENT We show that a novel vaccination modality combining an antigen-presenting cell-targeting glucan particle (GP) vaccine delivery system with encapsulated antigen (α-synuclein) + rapamycin (RAP) induced both strong anti-α-synuclein antibody titers and regulatory T cells (Tregs). This vaccine, collectively termed GP+RAP/α-syn, is capable of triggering neuroprotective Treg responses in synucleinopathy models, and the combined vaccine is more effective than the humoral or cellular immunization alone. Together, these results support the further development of this multifunctional vaccine approach for the treatment of synucleinopathies, such as Parkinson's disease, dementia with Lewy bodies, and multiple systems atrophy., (Copyright © 2018 the authors 0270-6474/18/381000-15$15.00/0.)

Coordinated regulation of innate immune responses is necessary in all metazoans. In Drosophila the Imd pathway detects Gram-negative bacterial infections through recognition of diaminopimelic acid (DAP)-type peptidoglycan and activation of the NF-κB precursor Relish, which drives robust antimicrobial peptide gene expression. Imd is a receptor-proximal adaptor protein homologous to mammalian RIP1 that is regulated by proteolytic cleavage and Lys-63-polyubiquitination. However, the precise events and molecular mechanisms that control the post-translational modification of Imd remain unclear. Here, we demonstrate that Imd is rapidly Lys-63-polyubiquitinated at lysine residues 137 and 153 by the sequential action of two E2 enzymes, Ubc5 and Ubc13-Uev1a, in conjunction with the E3 ligase Diap2. Lys-63-ubiquitination activates the TGFβ-activated kinase (Tak1), which feeds back to phosphorylate Imd, triggering the removal of Lys-63 chains and the addition of Lys-48 polyubiquitin. This ubiquitin-editing process results in the proteasomal degradation of Imd, which we propose functions to restore homeostasis to the Drosophila immune response., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

Bacterial sepsis involves a complex interaction between the host immune response and bacterial LPS. LPS binds Toll-like receptor (TLR) 4, which leads to the release of proinflammatory cytokines that are essential for a potent innate immune response against pathogens. The innate immune system is tightly regulated, as excessive inflammation can lead to organ failure and death. MicroRNAs have recently emerged as important regulators of the innate immune system. Here we determined the function of miR-718, which is conserved across mammals and overlaps with the 5' UTR of the interleukin 1 receptor-associated kinase ( IRAK1 ) gene. As IRAK1 is a key component of innate immune signaling pathways that are downstream of most TLRs, we hypothesized that miR-718 helps regulate the innate immune response. Activation of TLR4, but not TLR3, induced the expression of miR-718 in macrophages. miR-718 expression was also induced in the spleens of mice upon LPS injection. miR-718 modulates PI3K/Akt signaling by directly down-regulating phosphatase and tensin homolog (PTEN), thereby promoting phosphorylation of Akt, which leads to a decrease in proinflammatory cytokine production. Phosphorylated Akt induces let-7e expression, which, in turn, down-regulates TLR4 and further diminishes TLR4-mediated proinflammatory signals. Decreased miR-718 expression is associated with bacterial burden during Neisseria gonorrhoeae infection and alters the infection dynamics of N. gonorrhoeae in vitro Furthermore, miR-718 regulates the induction of LPS tolerance in macrophages. We propose a role for miR-718 in controlling TLR4 signaling and inflammatory cytokine signaling through a negative feedback regulation loop involving down-regulation of TLR4, IRAK1, and NF-κB., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

Purpose: To assess the influence of anodized titanium and zirconium dioxide abutments and peri-implant soft tissue thickness on the optical outcome of implant-supported lithium disilicate single crowns., Materials and Methods: Twenty patients with a missing maxillary single incisor, canine, or first premolar received an endosseous implant after a two-stage surgery protocol. After healing and soft tissue conditioning, peri-implant soft tissues were reproduced in the impression, and the thickness was measured. Customized abutments were made of titanium, gold-anodized titanium, pink-anodized titanium, and zirconium dioxide. The definitive prosthesis was a lithium disilicate crown stratified by feldsphatic porcelain. Customized abutments were screwed (35 Ncm), and the crown was temporarily placed on the abutment with a try-in paste. Color measurements were made using a spectrophotometer. CIELab color scale was employed following the formula: ΔE = (ΔL)² + (Δa) ² + (Δb) ². Data were analyzed using repeated-measures analysis of variance (ANOVA), Bonferroni and Pearson's correlation tests (α = .05)., Results: Abutment material type significantly affected the ΔE values at both the peri-implant soft tissue (P = .0001) and coronal level (P = .001). The lowest ΔE values were obtained with zirconia abutments at both soft tissue (6.06 ± 3.2) and coronal level (5.76 ± 2.9) compared with those of other abutments (soft tissue: 8.96 ± 3.1 to 11.56 ± 3.4; coronal: 8.66 ± 6.1 to 10.42 ± 6.3). Mean soft tissue thickness (1.63 ± 0.64 mm) affected the ΔE values at the peri-implant soft tissue level for only titanium and pink-anodized titanium abutments (P = .024 and P = .048, respectively). In all conditions, correlation coefficients between ΔE and the abutment materials were higher for titanium (r = -0.544; P = .024) and the least for zirconia (r = -0.313; P = .238) and gold-anodized titanium (r = -0.393; P = .119) abutments., Conclusion: All abutment types demonstrated noticeable color difference at both the soft tissue and coronal levels. Zirconia abutments showed the lowest ΔE values at both measurement zones. Soft tissue thickness did not affect the ΔE values at the peri-implant soft tissue level.